ESMERON 10MG/ML SOLUTION FOR INJECTION

Transcript

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For Position Only
SPC.ESM.14.UK.4126.II-UV96

10 mg/ml
solution for injection

o

ROCURONIUM BROMIDE

given when twitch height has recovered to 25% of control twitch height, or when 2 to
3 responses to train of four stimulation are present.
Continuous infusion
If rocuronium bromide is administered by continuous infusion, it is recommended to give
a loading dose of 0.6 mg/kg rocuronium bromide and, when neuromuscular block starts
to recover, to start administration by infusion. The infusion rate should be adjusted to
maintain twitch response at 10% of control twitch height or to maintain 1 to 2 responses
to train of four stimulation. In adults under intravenous anaesthesia, the infusion rate
required to maintain neuromuscular block at this level ranges from 0.3-0.6 mg/kg/h
(300-600 micrograms/kg/h) and under inhalational anaesthesia the infusion rate ranges
from 0.3-0.4 mg/kg/h. Continuous monitoring of neuromuscular block is essential since
infusion rate requirements vary from patient to patient and with the anaesthetic method
used.
Paediatric patients
For neonates (0-27 days), infants (28 days–2 months), toddlers (3-23 months), children
(2-11 years) and adolescents (12–17 years) the recommended intubation dose during
routine anaesthesia and maintenance dose are similar to those in adults.
However, the duration of action of the single intubating dose will be longer in neonates
and infants than in children (see section 5.1)
For continuous infusion in paediatrics, the infusion rates, with the exception of children
(2-11 years), are the same as for adults. For children aged 2-11 years higher infusion rates
might be necessary.
Thus, for children (2-11 years) the same initial infusion rates as for adults are
recommended and then this should be adjusted to maintain twitch response at 10% of
control twitch height or to maintain 1 or 2 responses to train of four stimulation during the
procedure.

1. NAME OF THE MEDICINAL PRODUCT
Esmeron 10mg/ml solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml Esmeron contains 10 mg rocuronium bromide.
For a full list of excipients, see 6.1.
3. PHARMACEUTICAL FORM
Solution for injection.
pH: 3.8-4.2
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Esmeron is indicated in adult and paediatric patients (from term neonaotes to
adolescents [0 to <18 years]) as an adjunct to general anaesthesia to facilitate
tracheal intubation during routine sequence induction and to provide skeletal
muscle relaxation during surgery. In adults Esmeron is also indicated to facilitate
tracheal intubation during rapid sequence induction and as an adjunct in the
intensive care unit (ICU) to facilitate intubation and mechanical ventilation.
4.2 Posology and method of administration
Posology
Like other neuromuscular blocking agents, Esmeron should only be administered
by, or under supervision of, experienced clinicians who are familiar with the action
and use of these drugs.
As with other neuromuscular blocking agents, the dosage of Esmeron should
be individualised in each patient. The method of anaesthesia and the expected
duration of surgery, the method of sedation and the expected duration of
mechanical ventilation, the possible interaction with other drugs that are
administered concomitantly, and the condition of the patient should be taken into
account when determining the dose.
The use of an appropriate neuromuscular monitoring technique is recommended
for the evaluation of neuromuscular block and recovery.
Inhalational anaesthetics do potentiate the neuromuscular blocking effects of
Esmeron. This potentiation however, becomes clinically relevant in the course of
anaesthesia, when the volatile agents have reached the tissue concentrations
required for this interaction. Consequently, adjustments with Esmeron should be
made by administering smaller maintenance doses at less frequent intervals or by
using lower infusion rates of Esmeron during long lasting procedures (longer than
1 hour) under inhalational anaesthesia (see section 4.5).
In adult patients the following dosage recommendations may serve as a general
guideline for tracheal intubation and muscle relaxation for short to long lasting
surgical procedures and for use in the intensive care unit.
Surgical Procedures
Tracheal intubation
The standard intubating dose during routine anaesthesia is 0.6 mg/kg rocuronium
bromide, after which adequate intubation conditions are established within
60 seconds in nearly all patients. A dose of 1.0 mg/kg rocuronium bromide
is recommended for facilitating tracheal intubation conditions during rapid
sequence induction of anaesthesia, after which adequate intubation conditions
are established within 60 seconds in nearly all patients. If a dose of 0.6 mg/kg
rocuronium bromide is used for rapid sequence induction of anaesthesia, it is
recommended to intubate the patient 90 seconds after administration of rocuronium
bromide.
For use of rocuronium bromide during rapid sequence induction of anaesthesia in
patients undergoing Caesarean section reference is made to section 4.6.
Higher doses
Should there be reason for selection of larger doses in individual patients, there
is no indication from clinical studies that the use of initial doses up to 2 mg/kg
rocuronium bromide is associated with an increased frequency or severity of
cardiovascular effects. The use of these high dosages of rocuronium bromide
decreases the onset time and increases the duration of action (see section 5.1).
Maintenance dosing
The recommended maintenance dose is 0.15 mg/kg rocuronium bromide;
in the case of long-term inhalational anaesthesia this should be reduced to
0.075-0.1 mg/kg rocuronium bromide. The maintenance doses should best be

The experience with rocuronium bromide in rapid sequence induction in paediatric
patients is limited. Rocuronium bromide is therefore not recommended for facilitating
tracheal intubation conditions during rapid sequence induction in paediatric patients.
Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure
The standard intubation dose for geriatric patients and patients with hepatic and/or biliary
tract disease and/or renal failure during routine anaesthesia is 0.6 mg/kg rocuronium
bromide. A dose of 0.6 mg/kg should be considered for rapid sequence induction of
anaesthesia in patients in which a prolonged duration of action is expected. Regardless
of the anaesthetic technique used, the recommended maintenance dose for these
patients is 0.075-0.1 mg/kg rocuronium bromide, and the recommended infusion rate is
0.3-0.4 mg/kg/h (see Continuous infusion). (See also section 4.4)
Overweight and obese patients
When used in overweight or obese patients (defined as patients with a body weight of
30% or more above ideal body weight) doses should be reduced taking into account ideal
body weight.
Intensive Care Procedures
Tracheal intubation
For tracheal intubation, the same doses should be used as described above under surgical
procedures.
Maintenance dosing
The use of an initial loading dose of 0.6 mg/kg rocuronium bromide is recommended,
followed by a continuous infusion as soon as twitch height recovers to 10% or upon
reappearance of 1 to 2 twitches to train of four stimulation. Dosage should always be
titrated to effect in the individual patient. The recommended initial infusion rate for the
maintenance of a neuromuscular block of 80-90% (1 to 2 twitches to TOF stimulation) in
adult patients is 0.3-0.6 mg/kg/h during the first hour of administration, which will need
to be decreased during the following 6-12 hours, according to the individual response.
Thereafter, individual dose requirements remain relatively constant.
A large between patient variability in hourly infusion rates has been found in controlled
clinical studies, with mean hourly infusion rates ranging from 0.2-0.5 mg/kg/h depending
on nature and extent of organ failure(s), concomitant medication and individual patient
characteristics. To provide optimal individual patient control, monitoring of neuromuscular
transmission is strongly recommended. Administration up to 7 days has been investigated.
Special populations
Esmeron is not recommended for the facilitation of mechanical ventilation in the intensive
care in paediatric and geriatric patients due to a lack of data on safety and efficacy.

cause residual neuromuscular blockade after extubation in the post-operative phase
(such as drug interactions or patient condition) should also be considered. If not used as
part of standard clinical practice, the use of a reversal agent (such as sugammadex or
acetylcholinesterase inhibitors) should be considered, especially in those cases where
residual neuromuscular blockade is more likely to occur.
High rates of cross-sensitivity between neuromuscular blocking agents have been
reported. Therefore, where possible, before administering Esmeron, hypersensitivity
to other neuromuscular blocking agents should be excluded. Esmeron should only be
used when absolutely essential in susceptible patients. Patients who experience a
hypersensitivity reaction under general anaesthesia should be tested subsequently for
hypersensitivity to other neuromuscular blockers.
Rocuronium may increase the heart rate.
In general, following long term use of neuromuscular blocking agents in the ICU,
prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help
preclude possible prolongation of neuromuscular block and/or overdosage it is strongly
recommended that neuromuscular transmission is monitored throughout the use of
neuromuscular blocking agents. In addition, patients should receive adequate analgesia
and sedation. Furthermore, neuromuscular blocking agents should be titrated to effect in
the individual patients by or under supervision of experienced clinicians who are familiar
with their actions and with appropriate neuromuscular monitoring techniques.
Myopathy after long term administration of other non-depolarising neuromuscular
blocking agents in the ICU in combination with corticosteroid therapy has been reported
regularly. Therefore, for patients receiving both neuromuscular blocking agents and
corticosteroids, the period of use of the neuromuscular blocking agent should be limited
as much as possible.
If suxamethonium is used for intubation, the administration of Esmeron should be delayed
until the patient has clinically recovered from the neuromuscular block induced by
suxamethonium.
The following conditions may influence the pharmacokinetics and/or
pharmacodynamics of Esmeron:
Hepatic and/or biliary tract disease and renal failure
Because rocuronium is excreted in urine and bile, it should be used with caution in
patients with clinically significant hepatic and/or biliary diseases and/or renal failure. In
these patient groups prolongation of action has been observed with doses of 0.6 mg/kg
rocuronium bromide.
Prolonged circulation time
Conditions associated with prolonged circulation time such as cardiovascular disease, old
age and oedematous state resulting in an increased volume of distribution, may contribute
to a slower onset of action. The duration of action may also be prolonged due to a reduced
plasma clearance.
Neuromuscular disease
Like other neuromuscular blocking agents, Esmeron should be used with extreme caution
in patients with a neuromuscular disease or after poliomyelitis since the response
to neuromuscular blocking agents may be considerably altered in these cases. The
magnitude and direction of this alteration may vary widely. In patients with myasthenia
gravis or with the myasthenic (Eaton-Lambert) syndrome, small doses of Esmeron may
have profound effects and Esmeron should be titrated to the response.
Hypothermia
In surgery under hypothermic conditions, the neuromuscular blocking effect of Esmeron is
increased and the duration prolonged.
Obesity
Like other neuromuscular blocking agents, Esmeron may exhibit a prolonged duration and
a prolonged spontaneous recovery in obese patients when the administered doses are
calculated on actual body weight.
Burns
Patients with burns are known to develop resistance to non-depolarising neuromuscular
blocking agents. It is recommended that the dose is titrated to response.
Conditions which may increase the effects of Esmeron
Hypokalaemia (e.g. after severe vomiting, diarrhoea and diuretic therapy),
hypermagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia,
dehydration, acidosis, hypercapnia, cachexia.
Severe electrolyte disturbances, altered blood pH or dehydration should therefore be
corrected when possible.
4.5 Interaction with other medicinal products and other forms of interaction

Method of administration
Esmeron is administered intravenously either as a bolus injection or as a continuous
infusion (see section 6.6).

The following drugs have been shown to influence the magnitude and/or duration of
action of non-depolarising neuromuscular blocking agents.

4.3 Contraindications

Increased effect:
• Halogenated volatile anaesthetics potentiate the neuromuscular block of Esmeron.
The effect only becomes apparent with maintenance dosing (see section 4.2).
Reversal of the block with acetylcholinesterase inhibitors could also be inhibited.
• After intubation with suxamethonium (see section 4.4).
• Long-term concomitant use of corticosteroids and Esmeron in the ICU may result in
prolonged duration of neuromuscular block or myopathy (see section 4.4 and 4.8).

Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients.
4.4 Special warnings and precautions for use
Since Esmeron causes paralysis of the respiratory muscles, ventilatory support is
mandatory for patients treated with this drug until adequate spontaneous respiration is
restored. As with all neuromuscular blocking agents, it is important to anticipate intubation
difficulties, particularly when used as part of a rapid sequence induction technique.
As with other neuromuscular blocking agents, residual neuromuscular blockade has
been reported for Esmeron. In order to prevent complications resulting from residual
neuromuscular blockade, it is recommended to extubate only after the patient has
recovered sufficiently from neuromuscular block. Geriatric patients (65 years or older)
may be at increased risk for residual neuromuscular block. Other factors which could

Recurarisation has been reported after post-operative administration of:
aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics,
quinidine, quinine and magnesium salts (see section 4.4).
Decreased effect:
• Prior chronic administration of phenytoin or carbamazepine.
• Calcium chloride, potassium chloride.
• Protease inhibitors (gabexate, ulinastatin).
Variable effect:
• Administration of other non-depolarising neuromuscular blocking
agents in combination with Esmeron may produce attenuation or
potentiation of the neuromuscular block, depending on the order of
administration and the neuromuscular blocking agent used.
• Suxamethonium given after the administration of Esmeron may produce
potentiation or attenuation of the neuromuscular blocking effect of
Esmeron.
Effect of Esmeron on other drugs
Esmeron combined with lidocaine may result in a quicker onset of action of
lidocaine.
Paediatric patients
No formal interaction studies have been performed. The above mentioned
interactions for adults and their special warnings and precautions for use
(see section 4.4) should be taken into account for paediatric patients.
4.6 Pregnancy and lactation
Pregnancy
For rocuronium bromide, no clinical data on exposed pregnancies are
available. Animal studies do not indicate direct or indirect harmful effects with
respect to pregnancy, embryonal/foetal development, parturition or postnatal
development. Caution should be exercised when prescribing Esmeron to
pregnant women.
Caesarean section
In patients undergoing Caesarean section, Esmeron can be used as part of
a rapid sequence induction technique, provided no intubation difficulties
are anticipated and a sufficient dose of anaesthetic agent is administered
or following suxamethonium facilitated intubation. However, Esmeron,
administered in doses of 0.6 mg/kg may not produce adequate conditions for
intubation until 90 seconds after administration. This dose has been shown
to be safe in parturients undergoing Caesarean section. Esmeron does not
affect Apgar score, foetal muscle tone or cardiorespiratory adaptation. From
umbilical cord blood sampling it is apparent that only limited placental transfer
of rocuronium bromide occurs which does not lead to the observation of clinical
adverse effects in the newborn.
Note 1: doses of 1.0 mg/kg have been investigated during rapid sequence
induction of anaesthesia, but not in Caesarean section patients. Therefore, only
a dose of 0.6 mg/kg is recommended in this patient group.
Note 2: Reversal of neuromuscular block induced by neuromuscular blocking
agents may be inhibited or unsatisfactory in patients receiving magnesium salts
for toxemia of pregnancy because magnesium salts enhance neuromuscular
blockade. Therefore, in these patients the dosage of Esmeron should be reduced
and be titrated to twitch response.
Lactation
It is unknown whether rocuronium bromide is excreted in human breast milk.
Animal studies have shown insignificant levels of rocuronium bromide in breast
milk.
Insignificant levels of rocuronium bromide were found in the milk of lactating
rats. There are no human data on the use of Esmeron during lactation. Esmeron
should be given to lactating women only when the attending physician decides
that the benefits outweigh the risks.
4.7 Effects on ability to drive and use machines
Since Esmeron is used as an adjunct to general anaesthesia, the usual
precautionary measures after a general anaesthesia should be taken for
ambulatory patients.
4.8 Undesirable effects
The most commonly occurring adverse drug reactions include injection site
pain/reaction, changes in vital signs and prolonged neuromuscular block. The
most frequently reported serious adverse drug reactions during post-marketing
surveillance is ‘anaphylactic and anaphylactoid reactions’ and associated
symptoms. See also the explanations below the table.
MedDRA SOC

1 What Esmeron is and what it is used for
Esmeron is one of a group of drugs called muscle relaxants.

Information for the patient

Muscle relaxants are used during an operation as part of a general anaesthetic. When you
have an operation your muscles must be completely relaxed. This makes it easier for the
surgeon to perform the operation.

10 mg/ml
solution for injection
ROCURONIUM BROMIDE

Normally, your nerves send messages called impulses to your muscles. Esmeron acts by
blocking these impulses so that your muscles relax. Because your breathing muscles also
relax, you will need help to breathe (artificial ventilation) during and after your operation
until you can breathe on your own again.

o

Read all of this leaflet carefully before you are given this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your anaesthetist.
• If any of the side effects gets serious, or if you notice any side effects not listed
in this leaflet, please tell your anaesthetist or doctor.
What is in this leaflet
1 What Esmeron is and what it is used for
2 Before Esmeron is given
3 How Esmeron is given
4 Possible side effects
5 How Esmeron is stored
6 Content of the pack and other information

During the operation your anaesthetist will keep a check on the effect of the muscle relaxant,
and if necessary will give you some more. At the end of surgery, the effects of the drug are
allowed to wear off and you will start breathing on your own. Sometimes the anaesthetist will
give you another drug to help speed this up.
Esmeron can also be used in Intensive Care Units to keep your muscles relaxed.
2 Before Esmeron is given
You should not receive Esmeron
• if you are allergic (hypersensitive) to rocuronium, the bromide ion or any of the
other ingredients of Esmeron.
➔

Tell your anaesthetist if this applies to you.

Take special care with Esmeron
Your anaesthetist needs to know before you receive this medicine:
• if you are allergic to muscle relaxants

•
•
•
➔

if you have had kidney, heart, liver or gall bladder disease
if you have had diseases affecting nerves and muscles
if you have fluid retention (oedema).
Tell your anaesthetist if any of these applies to you.

Some conditions may influence the effects of Esmeron — for example:
• low calcium levels in the blood
• low potassium levels in the blood
• high magnesium levels in the blood
• low levels of protein in the blood
• too much carbon dioxide in the blood
• loss of too much water from the body, for example by being sick, diarrhoea or
sweating
• over-breathing leading to too little carbon dioxide in the blood (alkalosis)
• general ill-health
• burns
• being very overweight (obesity)
• very low body temperature (hypothermia).
If you have any of these conditions, your anaesthetist will take it into account when
deciding the correct dose of Esmeron for you.
Children and Elderly
Esmeron can be used in children (newborns and adolescence) and elderly but your
anaesthetist should first assess your medical history.

Other medicines and Esmeron
➔ Tell your anaesthetist if you are taking other medicines or have recently
taken them. This includes medicines or herbal products that you have
bought without a prescription. Esmeron may affect other medicines or be
affected by them.
Medicines which increase the effect of Esmeron:
• certain antibiotics
• certain medicines for heart disease or high blood pressure (water tablets,
calcium channel blockers, beta-blockers and quinidine)
• certain anti-inflammatory medicines (corticosteroids)
• medicines for manic depressive illness (bipolar disorder)
• magnesium salts
• certain medicines used to treat malaria.
Medicines which decrease the effect of Esmeron:
• certain medicines for epilepsy
• calcium chloride and potassium chloride
• certain protease inhibitors called gabexate and ulinastatin.
In addition, you may be given other medicines before or during surgery which
can alter the effects of Esmeron. These include certain anaesthetics, other
muscle relaxants, medicines such as phenytoin and medicines which reverse
the effects of Esmeron. Esmeron may make certain anaesthetics work more
quickly. Your anaesthetist will take this into account when deciding the correct
dose of Esmeron for you.

MedDRA version 8.1
Anaphylaxis
Although very rare, severe anaphylactic reactions to neuromuscular blocking
agents, including Esmeron, have been reported. Anaphylactic/anaphylactoid
reactions are: bronchospasm, cardiovascular changes (e.g. hypotension,
tachycardia, circulatory collapse – shock), and cutaneous changes
(e.g. angioedema, urticaria). These reactions have, in some cases, been fatal.
Due to the possible severity of these reactions, one should always assume they
may occur and take the necessary precautions.
Since neuromuscular blocking agents are known to be capable of inducing
histamine release both locally at the site of injection and systemically, the
possible occurrence of itching and erythematous reaction at the site of injection
and/or generalised histaminoid (anaphylactoid) reactions (see also under
anaphylactic reactions above) should always be taken into consideration when
administering these drugs.
In clinical studies only a slight increase in mean plasma histamine levels has
been observed following rapid bolus administration of 0.3-0.9 mg/kg rocuronium
bromide.
Prolonged neuromuscular block
The most frequent adverse reaction to nondepolarising blocking agents as a
class consists of an extension of the drug’s pharmacological action beyond the
time period needed. This may vary from skeletal muscle weakness to profound
and prolonged skeletal muscle paralysis resulting in respiratory insufficiency or
apnea.
Myopathy
Myopathy has been reported after the use of various neuromuscular blocking
agents in the ICU in combination with corticosteroids (see section 4.4).
Local injection site reactions
During rapid sequence induction of anaesthesia, pain on injection has been
reported, especially when the patient has not yet completely lost consciousness
and particularly when propofol is used as the induction agent. In clinical studies,
pain on injection has been noted in 16% of the patients who underwent rapid
sequence induction of anaesthesia with propofol and in less than 0.5% of the
patients who underwent rapid sequence induction of anaesthesia with fentanyl
and thiopental.
Paediatric patients
A meta-analysis of 11 clinical studies in paediatric patients (n=704) with
rocuronium bromide (up to 1 mg/kg) showed that tachycardia was identified as
adverse drug reaction with a frequency of 1.4%.

Malta: ADR Reporting, The Medicines Authority, Post-Licensing Directorate,
203 Level 3, Rue D’Argens, GŻR-1368 Gżira. Website: www.medicinesauthority.gov.mt,
e-mail: postlicensing.medicinesauthority@gov.mt
4.9 Overdose
In the event of overdosage and prolonged neuromuscular block, the patient should
continue to receive ventilatory support and sedation. There are two options for the reversal
of neuromuscular block: (1) In adults, sugammadex can be used for reversal of intense
(profound) and deep block. The dose of sugammadex to be administered depends on
the level of neuromuscular block. (2) An acetylcholinesterase inhibitor (e.g. neostigmine,
edrophonium, pyridostigmine) or sugammadex can be used once spontaneous recovery
starts and should be administered in adequate doses. When administration of an
acetylcholinesterase inhibiting agent fails to reverse the neuromuscular effects of
Esmeron, ventilation must be continued until spontaneous breathing is restored. Repeated
dosage of an acetylcholinesterase inhibitor can be dangerous.
In animal studies, severe depression of cardiovascular function, ultimately leading to
cardiac collapse did not occur until a cumulative dose of 750 x ED90 (135 mg/kg rocuronium
bromide) was administered.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group (ATC code)
Muscle relaxants, peripherally acting agents. ATC code: M03AC09.
Mechanism of Action
Esmeron (rocuronium bromide) is a fast onset, intermediate acting non-depolarising
neuromuscular blocking agent, possessing all of the characteristic pharmacological
actions of this class of drugs (curariform). It acts by competing for nicotinic cholinoceptors
at the motor end-plate. This action is antagonised by acetylcholinesterase inhibitors such
as neostigmine, edrophonium and pyridostigmine.
Pharmacodynamic effects
The ED90 (dose required to produce 90% depression of the twitch response of the thumb to
stimulation of the ulnar nerve) during intravenous anaesthesia is approximately 0.3 mg/kg
rocuronium bromide. The ED95 in infants is lower than in adults and children (0.25, 0.35 and
0.40 mg/kg respectively).
The clinical duration (the duration until spontaneous recovery to 25% of control twitch
height) with 0.6 mg/kg rocuronium bromide is 30–40 minutes. The total duration (time until
spontaneous recovery to 90% of control twitch height) is 50 minutes. The mean time of
spontaneous recovery of twitch response from 25 to 75% (recovery index) after a bolus
dose of 0.6 mg/kg rocuronium bromide is 14 minutes. With lower dosages of 0.3-0.45 mg/kg
rocuronium bromide (1 -1½ x ED90), onset of action is slower and duration of action is shorter.
With high doses of 2 mg/kg, clinical duration is 110 minutes.
Intubation during routine anaesthesia
Within 60 seconds following intravenous administration of a dose of 0.6 mg/kg rocuronium
bromide (2 x ED90 under intravenous anaesthesia), adequate intubation conditions can be
achieved in nearly all patients of which in 80% intubation conditions are rated excellent.
General muscle paralysis adequate for any type of procedure is established within
2 minutes. After administration of 0.45 mg/kg rocuronium bromide, acceptable intubation
conditions are present after 90 seconds.
Rapid Sequence Induction
During rapid sequence induction of anaesthesia under propofol or fentanyl/thiopental
anaesthesia, adequate intubation conditions are achieved within 60 seconds in 93% and 96%
of the patients respectively, following a dose of 1.0 mg/kg rocuronium bromide. Of these, 70%
are rated excellent. The clinical duration with this dose approaches 1 hour, at which time
the neuromuscular block can be safely reversed. Following a dose of 0.6 mg/kg rocuronium
bromide, adequate intubation conditions are achieved within 60 seconds in 81% and 75%
of the patients during a rapid sequence induction technique with propofol or fentanyl/
thiopental, respectively.
Paediatric patients
Mean onset time in infants, toddlers and children at an intubation dose of 0.6 mg/kg is
slightly shorter than in adults. Comparison within paediatric age groups showed that the
mean onset time in neonates and adolescents (1.0 min.) is slightly longer than in infants,
toddlers and children (0.4, 0.6 and 0.8 min., respectively). The duration of relaxation and the
time to recovery tend to be shorter in children compared to infants and adults. Comparing
within paediatric age groups demonstrated that mean time to reappearance of T3 was
prolonged in neonates and infants (56.7 and 60.7 min., respectively) when compared to
toddlers, children and adolescents (45.4, 37.6 and 42.9 min., respectively).
Mean (SD) time to onset and clinical duration following 0.6 mg/kg rocuronium initial
intubating dose* during sevoflurane/nitrous oxide and isoflurane/nitrous oxide
(maintenance) anaesthesia (Paediatric patients) PP group
Time to maximum block **
(min)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance
of the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions (see details below)
Frequencies are estimates derived from post-marketing surveillance
reports and data from the general literature.
2
Post-marketing surveillance data cannot give precise incidence figures.
For that reason, the reporting frequency was divided over two rather than
five categories.
3
after long-term use in the ICU
1

Children (2-11 years)
0.84 (0.29)
37.58 (11.82)
n=34
Adolescents (12-17 years)
0.98 (0.38)
42.90 (15.83)
n=31
n=30
* Dose of rocuronium administered within 5 seconds.
** Calculated from the end of administration of the rocuronium intubating dose
Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure
The duration of action of maintenance doses of 0.15 mg/kg rocuronium bromide might
be somewhat longer under enflurane and isoflurane anaesthesia in geriatric patients
and in patients with hepatic and/or renal disease (approximately 20 minutes) than in
patients without impairment of excretory organ functions under intravenous anaesthesia
(approximately 13 minutes) (see section 4.2). No accumulation of effect (progressive
increase in duration of action) with repetitive maintenance dosing at the recommended
level has been observed.
Intensive Care Unit
Following continuous infusion in the Intensive Care Unit, the time to recovery of the train of
four ratio to 0.7 depends on the level of block at the end of the infusion. After a continuous
infusion for 20 hours or more the median (range) time between return of T2 to train of four
stimulation and recovery of the train of four ratio to 0.7 approximates 1.5 (1-5) hours in patients
without multiple organ failure and 4 (1-25) hours in patients with multiple organ failure.

Cardiovascular surgery
In patients scheduled for cardiovascular surgery the most common cardiovascular
changes during the onset of maximum block following 0.6-0.9 mg/kg rocuronium bromide
are a slight and clinically insignificant increase in heart rate up to 9% and an increase in
mean arterial blood pressure up to 16% from the control values.

If Esmeron is administered via the same infusion line that is also used for other
drugs, it is important that this infusion line is adequately flushed (e.g. with 0.9%
NaCl) between administration of Esmeron and drugs for which incompatibility
with Esmeron has been demonstrated or for which compatibility with Esmeron
has not been established.

Reversal of muscle relaxation
Administration of acetylcholinesterase inhibitors, (neostigmine, pyridostigmine or
edrophonium) at reappearance of T2 or at the first signs of clinical recovery, antagonises
the action of Esmeron.

6.3 Shelf life

5.2 Pharmacokinetic Properties
After intravenous administration of a single bolus dose of rocuronium bromide the plasma
concentration time course runs in three exponential phases. In normal adults, the mean
(95% CI) elimination half-life is 73 (66-80) minutes, the (apparent) volume of distribution at
steady state conditions is 203 (193-214) ml/kg and plasma clearance is 3.7 (3.5-3.9) ml/kg/min.
Rocuronium is excreted in urine and bile. Excretion in urine approaches 40% within
12-24 hours. After injection of a radiolabeled dose of rocuronium bromide, excretion of the
radiolabel is on average 47% in urine and 43% in faeces after 9 days. Approximately 50% is
recovered as the parent compound. No metabolites are detected in plasma.
Paediatric patients
Pharmacokinetics of rocuronium bromide in paediatric patients (n=146) with ages
ranging from 0 to 17 years were evaluated using a population analysis of the pooled
pharmacokinetic datasets from two clinical trials under sevoflurane (induction) and
isoflurane/nitrous oxide (maintenance) anesthesia. All pharmacokinetic parameters were
found to be linearly proportional to body weight illustrated by a similar clearance (l.hr-1.kg-1).
The volume of distribution (l.kg-1) and elimination half-life (h) decrease with age (years).
The pharmacokinetic parameters of typical paediatrics within each age group are
summarized below:
Estimated PK parameters (Mean [SD]) of rocuronium bromide in typical paediatric
patients during sevoflurane and nitrous oxyde (induction) and isoflurane/nitrous oxide
(maintenance anaesthesia)

PK
Parameters

CL (L/kg/hr)
Volume of
distribution
(L/kg)
T ½ β (hr)

Infants

Patient age range
Children
Toddlers

Adolescents

Term
newborn
infants
(0-27 days)

(28 days to
2 months)

0.31 (0.07)

0.30 (0.08)

0.33 (0.10)

0.35 (0.09)

0.29 (0.14)

0.42 (0.06)

0.31 (0.03)

0.23 (0.03)

0.18 (0.02)

0.18 (0.01)

1.1 (0.2)

0.9 (0.3)

0.8 (0.2)

0.7 (0.2)

0.8 (0.3)

(3-23 months) (2-11 years) (12-17 years)

Esmeron has a shelf life of 3 years, provided it is stored under the prescribed
conditions (see Special precautions for storage). The date mentioned on the
carton and on the label of the vial is the expiry date; this is the date up to which
Esmeron may be used. Since Esmeron does not contain a preservative, the
solution should be used immediately after opening the vial.
After dilution with infusion fluids (see section 6.6), chemical and physical in-use
stability has been demonstated for 72 hours at 30°C. From a microbiological point
of view, the diluted product should be used immediately. If not used immediately,
in-use storage times and conditions prior to use are the responsibility of the user/
administrator and would normally not be longer than 24 hours at 2 to 8°C, unless
dilution has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
Storage in the Refrigerator
Esmeron should be stored at 2°-8°C in the dark and used within the expiry date
given on the pack.
Storage out of the refrigerator
Esmeron may also be stored outside of the refrigerator at a temperature of up to
30°C for a maximum 12 weeks, after which it should be discarded. The product
should not be placed back into the refrigerator, once it has been kept outside. The
storage period must not exceed the shelf-life.
6.5 Nature and contents of containers
Esmeron 25 mg in 2.5 ml (10mg/ml)
Packaging of 10 vials each containing 25 mg rocuronium bromide.
Esmeron 50 mg in 5 ml (10mg/ml)
Packaging of 10 vials each containing 50 mg rocuronium bromide.
Esmeron 100 mg in 10 ml (10mg/ml)
Packaging of 10 vials each containing 100 mg rocuronium bromide.
Not all pack sizes may be marketed.
Type 1 Ph.Eur., clear, colourless, glass vial with a rubber closure and flip off cap.
The rubber stopper of the vial does not contain latex.

Geriatric patients and patients with hepatic and/or biliary tract disease and/or renal failure
In controlled studies the plasma clearance in geriatric patients and in patients with renal
dysfunction was reduced, in most studies however without reaching the level of statistical
significance. In patients with hepatic disease, the mean elimination half-life is prolonged
by 30 minutes and the mean plasma clearance is reduced by 1 ml/kg/min. (See section 4.2.)
Intensive Care unit
When administered as a continuous infusion to facilitate mechanical ventilation for 20 hours
or more, the mean elimination half-life and the mean (apparent) volume of distribution
at steady state are increased. A large between patient variability is found in controlled
clinical studies, related to nature and extent of (multiple) organ failure and individual patient
characteristics. In patients with multiple organ failure a mean (± SD) elimination half-life of
21.5 (± 3.3) hours, a (apparent) volume of distribution at steady state of 1.5 (± 0.8) l/kg and a
plasma clearance of 2.1 (± 0.8) ml/kg/min were found. (See section 4.2.)

In correspondence please quote batch number.
6.6 Special precautions for disposal and other handling
Compatibility studies with the following infusion fluids have been performed: In
nominal concentrations of 0.5 mg/ml and 2.0 mg/ml Esmeron has been shown to
be compatible with: 0.9% NaCl, 5% dextrose, 5% dextrose in saline, sterile water
for injections, Lactated Ringers and Haemaccel. Administration should be begun
immediately after mixing, and should be completed within 24 hours. Unused
solutions should be discarded.
7. MARKETING AUTHORISATION HOLDER
NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss, The Netherlands
8. MARKETING AUTHORISATION NUMBER
UK:
MALTA:

PL 05003/0041
MA 031/00201

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 15th July 1996
Date of latest renewal: 7th May 2002

5.3 Preclinical safety data

10. DATE OF REVISION OF THE TEXT

Effects in non-clinical studies were observed only at exposures considered sufficiently in
excess of the maximum human exposure indicating little relevance to clinical use.

August 2014

There is no proper animal model to mimic the usually extremely complex clinical situation
of the ICU patient. Therefore the safety of Esmeron when used to facilitate mechanical
ventilation in the Intensive Care Unit is mainly based on results obtained in clinical studies.

----------------!---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Pregnancy and breast feeding
➔ Tell your anaesthetist if you are pregnant or might be pregnant, or if you are
breast feeding.
Your anaesthetist may still give you Esmeron, but you need to discuss it first.
Esmeron may be given to you if you are having a Caesarean section.

If you are given more Esmeron than you need
As your anaesthetist will be monitoring your condition carefully it is unlikely that you will
be given too much Esmeron. However, if this happens, your anaesthetist will keep you
breathing artificially (on a ventilator) until you can breathe on your own. You will be kept
asleep while this takes place.

Driving and using machines
Do not drive or use machines until advised it is safe to do so. Because
Esmeron is given as part of a general anaesthetic, you may feel tired,
weak or dizzy for some time afterwards. Your anaesthetist will be able to
advise you on how long the effects are likely to last.

4 Possible side effects

3 How Esmeron is given
Dose
Your anaesthetist will work out the dose of Esmeron you need based on:
• the type of anaesthetic
• the expected length of the operation
• other drugs you are taking
• your state of health.
The normal dose is 0.6 mg per kg body weight and the effect will last
30–40 minutes.
How Esmeron is given
Esmeron will be given to you by your anaesthetist. Esmeron is given intravenously
(into a vein), either as single injections or as a continuous infusion (a drip).

For Position Only

Like all medicines, Esmeron can cause side effects, but not everybody gets them. If these
side effects occur while you are under anaesthetic, they will be seen and treated by your
anaesthetist.
Uncommon side effects
(up to 1 in 100 people given Esmeron are affected)
• the drug is too effective, or not effective enough
• the drug works for longer than expected
• lowering of blood pressure
• increase in heart rate
• pain near the site of injection.
Very rare side effects
(less than 1 in 10,000 people given Esmeron are affected)
• allergic (hypersensitivity) reactions (such as difficulty in breathing, collapse of the
circulation and shock)
• wheezing of the chest
• muscle weakness
• swelling, a rash or redness of the skin.

If any of the side effects gets serious
Or if you notice any side effects not listed in this leaflet:
➔ Tell your anaesthetist or other doctor.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any
possible side effects not listed in this leaflet. You can also report side effects directly
(see details below). By reporting side effects you can help provide more information on
the safety of this medicine.
United Kingdom: Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Malta: ADR Reporting, The Medicines Authority, Post-Licensing Directorate,
203 Level 3, Rue D’Argens, GŻR-1368 Gżira Website: www.medicinesauthority.gov.mt,
e-mail: postlicensing.medicinesauthority@gov.mt
5 How Esmeron is stored
The hospital will keep Esmeron according to the correct storage conditions, and will
ensure that it’s in its expiry date.
6 Contents of the pack and other information
What Esmeron contains
The active substance of Esmeron is rocuronium bromide 10 mg/ml.
The other ingredients are sodium acetate, sodium chloride, acetic acid and water for
injections. Each millilitre (ml) of Esmeron contains 1.72 mg of sodium.

What Esmeron looks like and contents of the pack
Esmeron is a colourless to slightly yellow/brown solution for injection. It is
available in vials containing 25 mg (10 vials per pack), 50 mg (10 vials per pack) or
100 mg (10 vials per pack) of rocuronium bromide.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder: NV Organon, Kloosterstraat 6, PO Box 20,
5340 BH Oss, The Netherlands.
Manufacturer: NV Organon, Kloosterstraat 6, PO Box 20, 5340 BH Oss,
The Netherlands
or Schering-Plough, Saint Charles, 60590 Eragny sur Epte, France.
Problems reading this leaflet?
To listen to or request a copy of this leaflet in Braille, large print or audio, please
call, free of charge:
0800 198 5000 (UK only).
Please be ready to give the following information:
Product name: Esmeron
Reference Number: PL 05003/0041
This is a service provided by the Royal National Institute of the Blind.
This leaflet was last revised in August 2014.

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.